Open forumDo childhood diseases affect NHL and HL risk? A case-control study from northern and southern Italy☆
Introduction
In most developed countries, Hodgkin lymphoma (HL) incidence has been stable, while that of non-Hodgkin lymphoma (NHL) has doubled over the past two decades [1], [2]. The risk for some lymphomas is known to increase following exposure to certain viral or bacterial infections [2], [3]. The only virus, thus far, established to be causally related to HL is the Epstein-Barr virus (EBV), with an approximately 40% attributable fraction [1], [4] and the demonstration that EBV genomes were present and expressed in the HD tumor cells (Reed-Sternberg cells) of a proportion of cases provided an important new understanding of the biology of the disease [5], [6]. For several infectious agents (HIV, HHV8, HTLV, HCV, and Helicobacter pylori) [2], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], on the contrary, exist only indirect evidence of positive association due to the capacity to elude the immune system [17]. The childhood infections may have the opposite (protective) effect on lymphoma risk because of a different age of infection and/or less severe infections. In fact since 1988 some studies reported a potential protective effect of measles and other childhood diseases for lymphoma and multiple myeloma [7], [8], [9], [18]. However, the etiology of most lymphomas is still unknown.
To further explore this topic, we investigated the potential association between NHL, HL, and a history of childhood diseases and mononucleosis using data from an Italian case-control study on lymphomas carried out in the province of Pordenone, northeast Italy, and in the city of Naples, southern Italy [13], [14].
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Material and methods
Between January 1999 and July 2002, we conducted a hospital-based case-control study in the province of Pordenone (northeast Italy) and in Naples (southern Italy). Details on study design are described elsewhere [13], [14]. Briefly, the present report looks at 225 histologically-confirmed incident NHL cases and 62 HL cases, aged 18 years or more. Controls were 504 inpatients admitted to the same hospitals as those with the lymphomas for a wide spectrum of acute conditions. Specifically excluded
Results
Education was negatively associated with HL (OR = 0.4, in the highest tertile compared to the lowest, 95% CI: 0.1–1.0), but not with NHL (OR = 1.2; 95% CI: 0.7–1.8); while place of birth (Southern Italy versus Northern Italy) demonstrated an association only to NHL risk (OR = 2.1; 95% CI: 1.2–3.6). No difference emerged between cases (both NHL and HL) and controls based on number of younger siblings. However, a negative association (OR = 0.6; 95% CI: 0.4–1.0) did emerge for NHL only when there were
Discussion
The etiological agents (viruses and bacteria) involved in the examined diseases are very different. Several studies have reported a positive association between mononucleosis and risk of HL, but so far present, the mechanisms through which other childhood infections in general may protect against HL and possibly NHL are unknown [1], [2], [20]. Early infection may promote the development of the immune system (particularly cell-mediated, Th1-type immunity), which may explain why young-adulthood
Conclusions
Our findings provide additional support to the hypothesis that infections by most common childhood pathogens may protect against HL [4], [34] or, at least, be correlated with some other early exposure, which may lower the risk of HL in adulthood. In addition, our study is one of the few study to provide evidence that measles may provide a protective effect against NHL [22], [23], [25], [35], particularly follicular B-cell lymphomas, which is in line with studies reporting that patients with
Acknowledgements
The authors wish to thank Drs. Marina Crovatto and Michele Spina for their collaboration in the study, Mrs. Olinda Volpato for study coordination, and Mrs. Luigina Mei for her editorial assistance.
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2012, Leukemia ResearchCitation Excerpt :Furthermore, many studies on subjects professionally exposed to infectious agents by repeated contacts with humans (barbers, hairdressers, teachers and care attendants) or animals (farmers and butchers) reported an excess risk of NHL [2]. Finally, some investigations pointed out a protective role of some infectious diseases occurring during childhood on the risk of developing lymphomas during adulthood [8–12]. This case-control study is aimed at evaluating the association between infectious diseases and risk of leukemia and NHL in an adult population.
Childhood infectious diseases and risk of multiple myeloma: An analysis of the Italian multicentre case-control study
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2020, Hematologic Malignancies
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This work was supported by grants from the A.I.R.C. (Italian Association for Cancer Research), the Ministry of Health F.S.N. 2002 Contract no. 122, and Compagnia di San Paolo (11582/23719).